What is the purpose of a Cystatin C (CysC) test?

Purpose of Cystatin C Test in Clinical Practice

Cystatin C testing is primarily used to more accurately estimate glomerular filtration rate (GFR) for diagnosing and confirming chronic kidney disease (CKD), particularly when creatinine-based estimates may be unreliable or when confirmation of CKD diagnosis is required. 1, 2

Key Functions of Cystatin C Testing

Primary Role in CKD Diagnosis

• Serves as a confirmatory test for CKD diagnosis, especially in adults with creatinine-based eGFR (eGFRcreat) of 45-59 ml/min/1.73 m² who lack other markers of kidney damage such as albuminuria 1, 2
• Part of the recommended "triple marker" panel (serum creatinine, serum cystatin C, and urine albumin-to-creatinine ratio) for optimal CKD diagnosis and staging 1

Advantages Over Creatinine

• More sensitive for detecting early renal impairment - can detect decreased GFR at earlier stages (around 88 ml/min/1.73 m²) compared to creatinine (75 ml/min/1.73 m²) 3
• Less influenced by non-renal factors such as:
  • Muscle mass
  • Gender
  • Age
  • Dietary factors 1, 2
• Provides race-neutral GFR estimation, eliminating the need for race-based adjustments required with creatinine 1, 2

Clinical Applications

Improved Risk Stratification

• Strengthens the association between eGFR and important clinical outcomes:
  • Cardiovascular events
  • Kidney failure
  • Mortality 1

Special Populations Where Cystatin C Is Particularly Valuable

• Elderly patients 1, 2
• Malnourished patients 2
• Cancer patients (especially for drug dosing calculations) 1, 2
• Patients with extreme body sizes 2
• Patients with reduced muscle mass 2

Medication Dosing

• Improves precision for drug dosing in patients with reduced renal function, particularly for:
  • Carboplatin
  • Topotecan 1

Clinical Implementation

When to Use Cystatin C

1. Initial CKD Diagnosis: When eGFRcreat is 45-59 ml/min/1.73 m² without albuminuria 1, 2
2. Special Populations: When creatinine-based eGFR may be less reliable due to:
   • Abnormal body habitus
   • Malnutrition
   • Extremes of age 2
3. Critical Treatment Decisions: When accurate GFR determination will significantly impact treatment 2

Interpretation Guidelines

• If eGFRcys or eGFRcreat-cys is <60 ml/min/1.73 m², CKD diagnosis is confirmed
• If eGFRcys or eGFRcreat-cys is ≥60 ml/min/1.73 m², CKD diagnosis is not confirmed 1, 2

Recommended Equations

• The combined creatinine-cystatin C equation (eGFRcreat-cys) generally provides the most accurate GFR estimate 2, 4
• For kidney transplant recipients, cystatin C-based equations have shown superior performance compared to creatinine-based equations 1

Limitations and Considerations

• Cystatin C may not be required for routine monitoring after CKD diagnosis is established 1
• Availability may be limited to reference laboratories rather than local facilities 5
• Cost considerations exist, though the combination of creatinine, cystatin C, and UACR is considered affordable in high-income settings 1

Clinical Impact

• Reduces misclassification of CKD - in a meta-analysis of 90,750 participants, 23% of persons with eGFR 60-74 ml/min/1.73 m² based on creatinine had eGFR <60 ml/min/1.73 m² based on cystatin C 1
• Improves detection of harmful acute and chronic changes in kidney function 4
• May reduce healthcare inequalities by providing race-neutral GFR estimation 2, 4

Cystatin C testing represents an important advancement in kidney function assessment that provides more accurate GFR estimation, particularly in populations where creatinine-based estimates are less reliable, and should be incorporated into clinical practice for CKD diagnosis and confirmation.